To minimize the systemic toxicity and short circulation of DOX, Rg3-PNPs and anti-PD-L1, while leveraging the collaborative therapeutic effect, we presented the localized chemo-immunotherapy based on thermo-sensitive hydrogels to boost the anti-tumor immunotherapeutic efficacy for 4T1 tumor (Scheme 1), which lacks estrogen receptor, progesterone receptor and human epidermal growth factor receptor2, regarded as a typically TNBC model [21]. The gene discussed is ESR1; the disease is neoplasm.